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Contractile activity of big endothelin‐1 on the human isolated bronchus
Author(s) -
Advenier C.,
Lagente V.,
Zhang Y.,
Naline E.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14429.x
Subject(s) - phosphoramidon , thiorphan , contraction (grammar) , neprilysin , endocrinology , medicine , enalapril , endothelin 1 , chemistry , bronchus , captopril , endothelin receptor , angiotensin converting enzyme , enzyme , biology , biochemistry , blood pressure , lung , respiratory disease , receptor
1 We have studied the contractile activity of the 39 amino acid precursor of endothelin‐1 (ET‐1), big endothelin‐1 (big ET‐1), on human isolated bronchi. The contribution of the metalloproteases, neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), in the presence or absence of the epithelium lining, by use of specific inhibitors, was also evaluated on the effects of big ET‐1. 2 Big ET‐1 elicited a potent contraction of human isolated bronchus. The –log EC 50 value for big ET‐1 was 7.53 ± 0.08 ( n = 11) and E max 78.5 ± 3.8% (% of ACh 3 m m ). 3 Incubation of human isolated bronchi with the NEP inhibitor phosphoramidon (10 −5 m ) induced a rightward shift of the concentration‐response curve induced by big ET‐1 (10 −9 m to 3 × 10 −7 m ). Similar results were observed when human bronchi were incubated with thiorphan (10 −5 m ), but the shift to the right was significantly less ( P < 0.01) than that observed in the case of phosphoramidon (−0.35 ± 0.05 vs — 0.67 ± 0.07 log unit). 4 The two inhibitors of angiotensin I converting enzyme (ACE), captopril or enalapril diacid, did not affect the concentration‐response curve for contraction induced by big ET‐1. 5 When the epithelium was removed, a leftward shift of the concentration‐response curve of big ET‐1 (10 −9 m to 3 × 10 −7 m ) was observed. Incubation of human isolated bronchi with phosphoramidon or thiorphan (10 −5 m ) or with enalapril diacid or captopril did not modify the leftward shift of the concentration‐response curve for big ET‐1 after epithelium removal. 6 These results suggest that big ET‐1 elicits potent contractile activity in the human isolated bronchus and that its effect is the consequence of the conversion to ET‐1 by a phosphoramidon‐sensitive metalloprotease which, although different from NEP and ACE, appears to be similar to the endothelin‐converting enzyme (ECE) described in other studies in animals.